The present invention relates to a tricyclic indole-2-carboxylic acid compound which is a potent N-methyl-D-aspartate (NMDA) receptor antagonist.
JP 7-188166-A (EP 657427; U.S. Pat. No. 5,496,843) discloses tricyclic indole-2-carboxylic acid derivatives useful as NMDA receptor antagonists. WO 97/38681 (EP 903144) discloses that some tricyclic nitrogen-containing compounds are useful for treating retinal neuropathy. However, those documents do not disclose specifically the tricyclic indole-2-carboxylic acid compound of the present invention.
The present invention is intended to provide a potent NMDA receptor antagonist. The present inventors found that the tricyclic indole-2-carboxylic acid compound of the present invention is a potent NMDA receptor antagonist and has efficient anti-convulsive activities. Thus, the present invention has been accomplished.
That is, the present invention provides a compound which is a tricyclic indole-2-carboxylic acid of formula(1): 
or a prodrug thereof, or a pharmaceutically acceptable salt of the said acid or prodrug, or a solvate of the said acid, prodrug or salt.
In one aspect of the invention the compound is a hydrochloride monohydrate represented by formula(2): 
Preferably the monohydrate of formula (2) has a powder X-ray diffraction pattern having average values of diffraction angle(2xcex8) and relative intensity as given by the following table:
The present invention further provides a compound of the invention as defined above for use in a method of treatment of the human or animal body by therapy.
The invention also provides a pharmaceutical composition comprising a compound of the invention as defined above and a pharmaceutically acceptable carrier or diluent.
In one embodiment the compound of the invention as defined above is for treating damage to the central nervous system induced by ischemic or hypoxic conditions.
In a second embodiment the compound of the invention as defined above is for treating damage to the central nervous system induced by a stroke.
In a third embodiment the compound of the invention as defined above is for treating convulsions.
The present invention further provides the use of a compound of the invention as defined above in the preparation of a medicament for treating damage to the central nervous system induced by ischemic or hypoxic conditions.
The invention also provides a method of treating damage to the central nervous system induced by ischemic or hypoxic conditions which comprises administering a compound of the invention as defined above to a patient in need thereof.